Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia.
In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing?±?50g of the corresponding fat blend.
Postprandial concentrations of triacylglycerol (diet-effect -?0.18mmol/L; p?=?0.001) and apolipoprotein B48 (diet-effect -?0.68mg/L; p?=?0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC) and first meal (iAUC) responses were lower after stearic-acid intake (p???0.01). Second meal responses (iAUC) were not different. Postprandial changend those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016.Savolitinib is an oral, potent, and highly selective MET-tyrosine kinase inhibitor under investigation in various tumor types. A thorough QT study evaluated effects on QT interval after a 600-mg single savolitinib dose in healthy subjects. We report exposure-response (E-R) modeling from this study to characterize the effects of savolitinib and its metabolites, M2 and M3, on QTc changes. In a novel application, in vitro potencies against hERG current provided mechanistic support to model the metabolites' effects. The hERG IC50 estimates (95% CI) were 25.8 (22.2-29.9) and 22.6 (14.7-34.6) μM for parent and M2, respectively. The E-R was described by both linear and Emax models, with exposure captured by an active moiety that consisted of savolitinib and M2 concentrations, weighted by the hERG IC50 ratio (1.14). The maximal increase in ΔΔQTcF and EC50 estimates (95% CI) was 18.5 (9.2-27.7) ms and 5709 (2889-8529) nM, respectively. Ignoring M2 contribution resulted in under prediction of QTcF prolongation in the hypothetical case of inhibited M2 clearance; at 300 mg Cmax, the mean (90% CI) of ??QTcF was 9.0 (5.7-12.6) and 5.9 (2.9-8.9) ms using the hERG-informed and parent-only linear models, respectively. Simulations in normal setting confirmed modest QTcF prolongation with 600 mg, but not 300 mg. Using the linear model, the mean (90% CI) maximum ΔΔQTcF were 12.3 (8.6-16.2) and 5.5 (2.6-8.5) ms for 600 and 300 mg, respectively. Further clinical studies will monitor cardiac safety to assess the clinical significance of QT-interval prolongation with savolitinib.To develop a prediction model that combined magnetic resonance images (MRI)-based radiomics features with clinical factors to predict recurrence-free survival (RFS) of hepatocellular carcinoma (HCC) patients treated with surgical resection.
HCC patients treated with surgical resection (n = 153) were randomly divided into training (n = 107) and validation (n = 46) datasets. The volumes of interest were manually outlined around the lesion and additional 2 mm and 5 mm peritumoral areas were created with automated dilatation in MRI to extract tumoral (T) and peritumoral (PT) radiomics features. The radiomics models were constructed using least absolute shrinkage and selection operator Cox regression. The combined model incorporated clinical factors and radiomics features using multivariable Cox regression based on the Akaike information criterion principle. Predictive performance of different models were evaluated by receiver operating characteristic (ROC) curves, decision curves, and calibration curves.
Among the radiomics models, similar performance was observed in the 2 mm and 5 mm PT models (C-index both 0.657), which were better than the T model or T + PT model (C-index 0.607 and 0.641, respectively) in the validation dataset, whereas the model combined with the three identified clinical risk factors showed the best performance (C-index 0.725). Results of the ROC curves, decision curves, and the calibration curves indicated that the combined model and the derived nomogram had better prediction performance, greater clinical benefits, and fair calibration efficiency.
The prediction model that combined MRI radiomics signatures with clinical factors can effectively predict the prognosis of patients with HCC treated with surgical resection.
The prediction model that combined MRI radiomics signatures with clinical factors can effectively predict the prognosis of patients with HCC treated with surgical resection.Refractory bile leaks represent a damaging sequela of hepatobiliary surgery and direct trauma. Management of bile leaks represents a challenging clinical problem. Despite advances in endoscopic techniques, interventional radiology continues to play a vital role in the diagnosis and management of refractory bile leaks. This article reviews strategies for optimizing the diagnosis and management of bile leaks and provides an overview of management strategies, including the management of complicated biliary leaks.Although zinc deficiency is common among dialyzed patients, its prevalence among non-dialyzed subjects and its relationship to renal function remain unclear.
We selected 816 non-dialyzed subjects (495 males; mean age, 56?±?18years) who underwent measurement of serum zinc at Jikei University Hospital between April 2018 and March 2019 using the Standardized Structured Medical Information eXchange2 (SS-MIX2) system, a global standard in Japan that enables collection of structured medical records with automatic data transfer to a registry database system. A serum zinc level of 60-80μg/dL was defined as marginal zinc deficiency and a level of?&lt;?60μg/dL as absolute zinc deficiency. https://www.selleckchem.com/peptide/box5.html We investigated factors associated with serum zinc using multiple regression analysis.
Marginal and absolute zinc deficiency were present in 52.3% and 30.6% of subjects, respectively. Serum zinc levels tended to decrease with increasing stage of chronic kidney disease (CKD) (P?=?0.051). Estimated glomerular filtration rate (eGFR) was not independently associated with serum zinc levels.